Age-related decline in plasma testosterone is an established but poorly understood phenomenon in human males. Detailed investigation of possible causes of an age-related decline in androgen status may be explored in a species such as the laboratory rat, which also exhibits a reduction in circulating testosterone with advancing age. The major objective of the proposed research is determination of the extent to which diminishing plasma testosterone levels in aging rats may be explained by changes in testicular Leydig cells functioning under gonadotropic regulation. This investigation of declining androgen status will consider the possible contribution of factors such as declining levels of circulating gonadotropin, inadequate access of circulating gonadotropin or other essential metabolic factors to the Leydig cell, reduction in the absolute abundance of Leydig cells, reduction in the abundance or binding affinity of gonadotropin receptors on the Leydig cell membrane, and intrinsic changes in the activity of the androgenic pathway within Leydig cells. At the same time, ultrastructural correlates of the aging process in Leydig cells will be sought through careful observation of the cell membrane, smooth endoplasmic reticulum, mitochondria, lysosomes, peroxisomes, and residual bodies. Investigative techniques used in this project include radioimmunoassay of gonadotropin and testosterone, radioligand-receptor assay of gondadotropin binding sites on Leydig cell membranes, metabolic pathway assessment using radiolabeled substrates, and light and electron microscopic evaluation of the abundance and structural features of Leydig cells.